CONTENTS
- INTROCUTION
- TYPES OF PARKINSON’S DISEASE
- PATHOPHYSIOLOGY OF PARKINSON’S DISEASE
- TREATMENT OF PARKINSON’S DISEASE
- ANIMALS MODELS OF PARKINSON’S DISEASE
- REFERENCES
1. INTROCUTION
Parkinson’s disease is a chronic, progressive neurodegenerative disorder. Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% and 2% of the population over the age of 65 and 80 respectively (Walker and Edwards, 2003).
The main pathological mechanism of this disease is damage to dopaminergic neurons in the substantia nigra pars compacta (SNpc) resulting in a specific dys-organisation of the complicated basal ganglia circuits. These neurons are required for appropriate motor function, and their loss is associated with symptoms, such as tremors, rigidity, bradykinesia and postural instability. The abnormal lewy bodies formation, oxidative stress, inhibition of mitochondrial complex-1 are identified as the primary mechanism involved in the development of Parkinson’s disease. It is not clear why Lewy body formation causes neuronal cell death. These pathological changes are seen in the locus coeruleus and autonomic and postganglionic neurons, pedunculopontine nucleus, raphe nucleus, and dorsal motor nucleus of the vagal nerve.
The dopamine depletion theory was confirmed by post mortem biochemical studies on PD patients showing decreased levels of dopamine and its metabolites in the nucleus caudatus, putamen, nucleus accumbens, substantia nigra and globus. (Horny, 2006). Parkinsonian symptoms occur under wide variety of conditions (Gybels, 1994) as in post encephalitic Parkinsonism and certain drugs also produce Parkinsonian symptoms such as DA receptor blocking agents used in the treatment of Schizophrenia (Robert et al., 1997)
L-dopa is the most efficacious antiparkinsonian drug and virtually all patients respond to its administration. However, a major limitation to the chronic use of L-dopa is the development of motor complications such as motor fluctuations and dyskinesia (Lang & Lozano, 1998). Parkinson’s disease is mainly connected to excessive oxidative stress that damages brain areas and triggers the process of neurodegeneration, especially in the nigrostriatal region. This process is crucial breakpoint for controlling the disease.
2. TYPES OF PARKINSON’S DISEASE
PD is broadly classified in to primary and secondary Parkinsonism. Majority of patients 80-85% diagnosed with PD are of primary Parkinsonism.
Primary Parkinsonism
It is also called as idiopathic Parkinson’s disease, which means disease with unknown cause. This type tends to respond well to drugs that work by increasing or substituting dopamine molecules in the brain.
Secondary Parkinsonism
It is also called as “atypical Parkinsonism or Parkinson’s plus”. In these cases, the cause of the disease is generally known. Although it is very difficult to differentiate idiopathic Parkinson’s disease and secondary parkinsonism, a key difference is that patients with secondary parkinsonism do not respond well to dopaminergic medications such as Levodopa.
Secondary Parkinsonism includes:
- Drug induced parkinsonism
- Vascular induced parkinsonism
- Normal pressure hydrocephalus
- Cortico-basal degeneration
- Progressive supranuclear palsy (PSP)
- Multiple system atrophy (MSA)
Drug Induced Parkinsonism
About 7% of people with Parkinsonism develops their symptoms following treatment with particular medications. Certain medications, such as antipsychotics, results in the patient developing the symptoms of Parkinson’s disease. Drug induced may be difficult to distinguish from Parkinson’s disease, but the symptoms of tremors and postural instability will generally improve in the weeks or months after stopping the medication (Hubble, 1993).
Vascular Parkinsonism
Vascular parkinsonism (VP) is most frequently presented as lower body parkinsonism, a condition that is accompanied by the development of white matter lesions (WMLs) and lacunes in the brain (Fitz et al., 1989). Patients with lower body parkinsonism exhibit gait impairment and go on to develop urinary incontinence, abnormal pyramidal responses and cognitive decline. Other clinical features include having abnormal glabellar tap responses, seen as persistent blinking in response to repetitive tapping on the forehead, and frontal release signs, such as snout or palmo- mental reflexes, are occasionally present (Okuda et al., 2008)
This type of Parkinsonism is caused by a series of small strokes, resulting in the death of parts of the brain, leading to the Parkinson’s disease-like symptoms. It tends to be less responsive to typical Parkinson’s disease medication especially as it progresses to Vascular Parkinson’s disease becomes more common with age, especially in people with diabetes (Korczyn , 2015).
Normal Pressure Hydrocephalus (NSA)
The symptoms of normal pressure hydrocephalus are very similar to those seen in vascular Parkinsonism. The condition is treated by removing spinal fluid in the short term or by lumbar puncture to permanently divert the spinal fluid as a long-term treatment.Cortico-Basal Degeneration (CBD) CBD is caused by a build-up of proteins called tau, which damages parts of the brain. The condition tends to start on one side of the body and slowly spread to other areas over time. This is the least common cause of the atypical parkinsonism. Clinical features are progressive asymmetrical rigidity and apraxia. Symptoms typically begin in one limb (no predilection for the right or left side has been observed). Patients describe their limb difficulties as “clumsiness,” “incoordination,” or “stiffness.” On examination, the limb is mildly to severely rigid and sometimes adopts a dystonic posture. Features of both rigidity velocity-independent increased tone) and spasticity (velocity-dependent increased tone) can be present in the affected limbs (Riley et al.,
Impressum
Verlag: BookRix GmbH & Co. KG
Tag der Veröffentlichung: 05.07.2019
ISBN: 978-3-7487-0925-1
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